Moira M. Rachman

On 489 evaluable new Mac1 complexes, AlphaFold3, Chai-1 and Boltz-2 placed over half of ligands within 2 Å, but on docking hit-lists AF3 and Boltz-2 added little over docking.

This study uses library docking to identify subtype-selective CB2 receptor ligands, finding improved hit rates and affinities with larger libraries and structure-based optimization.

This study systematically evaluates the effectiveness of random small perturbations in ligand optimization, finding 11.2% of analogs improved potency by ≥10-fold but often had worse pharmacokinetics.

This paper identifies AVI-6451, an orally bioavailable inhibitor of SARS-CoV-2 Mac1 with once-daily efficacy in a mouse model.

This study identifies Mac1 as a therapeutic target for SARS-CoV-2 and demonstrates that AVI-4206, a small molecule inhibitor, reduces viral replication and improves survival in an animal model.

The paper analyzes the structural and dynamic differences between ChikV Mac1 and SARS-CoV-2 Mac1 to explain differences in ligand binding affinity and designs inhibitors for ChikV Mac1.

Shape-based fragment merging (FrankenROCS) with Thompson sampling over 22 billion molecules found neutral SARS-CoV-2 macrodomain inhibitors; analogs reached single-digit micromolar IC50, backed by 137 crystal structures.